This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective is to develop and deploy novel, web accessible, cluster-enabled, grid-aware software and data resources that allow investigators in biomechanics, biophysics and cardiovascular physiology to perform numerical experiments that are: structurally integrated from sub-cellular to whole organ scales;functionally integrated across interacting biological processes;and that integrate experimental data from a variety of sources, scales and modalities. We will explore and advance the synthesis of these integrative analyses so that investigators can develop computational models that integrate theory with empirical data both functionally and structurally to investigate experimentally motivated biomedical hypotheses. To achieve these goals, we propose to interact closely with the visualization, grid computing and data integration core research activities of the resource. To focus these developments on scientifically important questions, we have developed collaborative projects with investigators who are applying experimental and computational approaches to understand the cellular and molecular mechanisms of physiological and pathophysiological processes that are dependent on the three-dimensional anatomy of the whole heart for their manifestations in vivo. The primary application of this core will continue to be computational models of cardiac electromechanical properties that integrate from single myocyte biophysics to whole heart physiology and are validated with experimental measurements in well characterized animal models. Whereas the data components of these multiscale models and their experimental validation are specific to the heart, the computational methods and software are more general. Therefore, the aims of the renewal and the targeted users of the new tools under development extend beyond the biophysics of the heart to other biomedical applications including soft tissue biomechanics, electrophysiology, systems biology, and diagnostic medical imaging. Aim 1: Interactive High-Performance Modeling Environment for Dynamic Authoring of Integrative Multi-Scale Models Aim 2: Multi-Scale Model Repository and Sharing Framework Aim 3: Software for Patient-Specific Diagnosis and Treatment of Heart Disease Supplemental Aim D Expediting Patient Specific Modeling and Continuity Development: Capitalizing on new NIH investments since NBCR renewal submission to help build an emerging community or researchers D1. Expedite the development of patient-specific multi-scale modeling software proposed in Aim 3 D2. Develop a database of de-identified patient-specific models using the new tools and newly available clinical data, and to accelerate the development and release of the multi-scale model repository and sharing framework proposed in Aim 2 D3. Harness GPU technology to speed up key codes in Continuity